Upon infection of cells by retroviruses, a large-size viral nucleoprotein complex is observed in the cytoplasm. These complexes vary in size from 160S for murine leukemia virus (MLV) to 80S for human immunodeficiency virus (HIV) type-1. The viral nucleoprotein complexes contain newly synthesized blunt-ended linear viral DNA that is subsequently trimmed by two nucleotides at its 3' termini by the viral integrase(IN). IN can catalyze the concerted integration of the recessed viral DNA termini into exogenous DNA targets (full-site reaction) mimicking the in vivo reaction. Both the trimming and integration of the viral DNA by IN in the nucleoprotein complexes requires the metal cofactor Mg.sup.2+.
Similar trimming and integration reactions can also be catalyzed by purified IN in vitro. IN derived from bacterial expression systems or purified from avian myeloblastosis virus (AMV) can trim two nucleotides from the termini of oligonucleotides or DNA restriction fragments containing viral long terminal repeat (LTR) sequences . The recessed DNA substrates can then be integrated into other DNA targets by IN. The majority of the observed integration events with these substrates involve the insertion of a single LTR terminus into one strand of the target DNA (half-site reaction). Expressed IN requires Mn.sup.2+ for efficient catalysis of either the trimming or the strand transfer reactions while AMV IN can effectively use Mg.sup.2+ or Mn.sup.2+ for these reactions. To date, expressed IN is not capable of efficiently performing the concerted insertion of viral-like DNA substrates into target DNA using either divalent